Congenital syphilis is a major cause of pregnancy loss and stillbirth as well as infant morbidity, and the incidence of congenital syphilis continues to dramatically rise in the United States. Infants may present with signs of congenital infection including hepatosplenomegaly, rash, and osteochondritis/periostitis. However, most infants at risk for congenital syphilis are asymptomatic in the newborn period. Diagnosis is based on maternal serologic testing as well as thorough infant evaluation, including physical examination, complete blood cell and platelet counts, cerebrospinal fluid analysis, and long bone imaging. Treatment with penicillin is curative; duration of therapy depends on timing of maternal treatment (if any) and results of the infant’s evaluation. Prevention of congenital syphilis requires timely screening and treatment during pregnancy.